Combined Anserine/Carnosine Exerts Anti‐Hyperuricemic, Nephroprotective, and Gut Microbiota‐Modulating Effects in Hyperuricemia Mice

The anti‐hyperuricemic, nephroprotective, and gut microbiota modulation effects of mixed carnosine and anserine (MAC) with the fixed ratio of 10:1 were evaluated in the hyperuricemic model mouse. The low‐ and high‐dose (1.6 and 8.3 mg/kg BW) of MAC could significantly reduce serum uric acid (UA) level by 58% and 56%, close to the normal level, respectively. The MAC significantly inhibited xanthine oxidase activity in both hepatic tissue and serum. Furthermore, MAC treatment ameliorated the renal injury indicated by the normalized serum creatinine and urea nitrogen levels, recovered histopathological characteristics, mitigated oxidative stress, and suppressed proinflammatory cytokines. Notably, MAC could accelerate UA excretion by markedly downregulating the expression of the URAT1 and GLUT9, while upregulating the transporter OAT1. Gut microbiota analysis demonstrated that MAC restored intestinal microbial diversity in hyperuricemic mice and reduced the abundance of genera linked to hyperuricemia and inflammation. All the results proved MAC as potential UA‐lowering treatment.